ArticleJournal of experimental & clinical cancer research : CR2022
Safety, recommended dose, efficacy and immune correlates for nintedanib in combination with pembrolizumab in patients with advanced cancers.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02856425 (Phase Ib Trial Of Pembrolizumab And Nintedanib), which is not on this map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase Ib Trial Of Pembrolizumab And Nintedanib
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- The association between interleukin-8 gene polymorphism and the risk of sepsis in older adults.Journal of orthopaedic surgery and research · 2024Pooled it
- Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer (NECTAR): a multi-center phase 2 study.Signal transduction and targeted therapy · 2024Trial
- TGF-β Inhibitor Potentiates Osimertinib-Induced Anti-Tumor Immunity in Egfr-Mutant Lung Cancer.Cancer science · 2026Article
- Nintedanib enhances the antitumor efficacy of pd-1 blockade, potentially through inhibition of myeloid-derived suppressor cells and cancer-associated fibroblasts.Cancer immunology, immunotherapy : CII · 2026Article
- Circulating T-lymphocyte subsets as biomarkers for immune checkpoint inhibitors in solid tumors.Clinical and experimental immunology · 2026Review
- Real-world efficacy, safety, and associated biomarkers of cadonilimab in cervical cancer: a prospective observational study.Frontiers in immunology · 2026Observational
- Inflammation in hepatocellular carcinoma progression: a "Single Wick, dual interwoven strands" regulatory framework.Frontiers in immunology · 2026Review
- Endothelial cell in tumor angiogenesis: Origins, mechanisms, and therapeutic implication.Genes & diseases · 2025Review
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Polymeric Polylactic Acid-Glycolic Acid-Based Nanoparticles Deliver Nintedanib Across the Blood-Brain Barrier to Inhibit Glioblastoma Growth.International journal of molecular sciences · 2025Article
- Vascular Endothelial Growth Factor (VEGF) Family and the Immune System: Activators or Inhibitors?Biomedicines · 2024Review
- Article
- Circulating T cells: a promising biomarker of anti-PD-(L)1 therapy.Frontiers in immunology · 2024Review
- Review
- Improvements in Systemic Therapies for Advanced Malignant Mesothelioma.International journal of molecular sciences · 2023Review
- Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti-PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma.Cancer discovery · 2023Article
- Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Efficacy and safety of nintedanib in patients with non-small cell lung cancer, and novel insights in radiation-induced lung toxicity.Frontiers in oncology · 2023Review
- Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.Frontiers in immunology · 2023Review
- Surgical and oncological management of renal medullary carcinoma in a young patient: a case report.Frontiers in oncology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe aimed to determine the safety and efficacy of nintedanib, an oral anti-angiogenic tyrosine kinase inhibitor, in combination with pembrolizumab, an anti-PD1 immunotherapy, in patients with advanced solid tumors (PEMBIB trial; NCT02856425).
methodsIn this monocentric phase Ib dose escalation cohort, we evaluated escalating doses of nintedanib (Dose level 1 (DL1) = 150 mg bid [bis in die, as twice a day]; DL2 = 200 mg bid, oral delivery) in combination with pembrolizumab (200 mg Q3W, IV). Patients received a 1-week lead-in dose of nintedanib monotherapy prior starting pembrolizumab. The primary objective was to establish the maximum tolerated dose (MTD) of the combination based on dose limiting toxicity (DLT) occurrence during the first 4 weeks. Secondary objectives were to assess the anti-tumor efficacy and to identify the associated immune and angiogenic parameters in order to establish the recommended nintedanib dose for expansion cohorts. Flow cytometry (FC), Immuno-Histo-Chemistry (IHC) and electrochemiluminescence multi-arrays were prospectively performed on baseline & on-treatment tumor and blood samples to identify immune correlates of efficacy.
resultsA total of 12/13 patients enrolled were evaluable for DLT (1 patient withdrew consent prior receiving pembrolizumab). Three patients at 200 mg bid experienced a DLT (grade 3 liver enzymes increase). Four patients developed grade 1-2 immune related adverse events (irAE). Eight patients died because of cancer progression. Median follow-up was 23.7 months (95%CI: 5.55-40.5). Three patients developed a partial response (PR) (ORR = 25%) and five patients (42%) had durable clinical benefit (DCB), defined as PR or stable disease (SD) ≥ 6 months. At baseline, patients with DCB had higher plasma levels of Tie2, CXCL10, CCL22 and circulating CD4
conclusionNintedanib 150 mg bid is the recommended dose for combination with pembrolizumab and is currently investigated in multiple expansion cohorts. Early tumoral and circulating immune factors were associated with cancer outcome under nintedanib & pembrolizumab therapy.
trial registrationClinicalTrials.gov, NCT02856425 . Registered August 4, 2016 - Prospectively registered.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.